ACADM

The ACADM gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase (MCAD). This enzyme functions within mitochondria, the energy-producing centers in cells. MCAD is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.

MCAD is required to metabolize a group of fats called medium-chain fatty acids. These fatty acids are found in foods and body fat and are produced when larger fatty acids are metabolized. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues.

medium-chain acyl-CoA dehydrogenase deficiency - caused by mutations in the ACADM gene

More than 80 mutations in the ACADM gene have been found to cause medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Many of these mutations change single protein building blocks (amino acids) in the MCAD enzyme. The most common change replaces the amino acid lysine with the amino acid glutamic acid at position 304 in the enzyme (written as Lys304Glu or K304E). This mutation and other amino acid substitutions alter the enzyme's structure, severely reducing or eliminating its activity. Other types of mutations lead to an abnormally small and unstable enzyme that cannot function.

With a shortage (deficiency) of functional MCAD enzyme, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to some features of this disorder such as lack of energy (lethargy) and low blood sugar (hypoglycemia). Medium-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver and brain. This abnormal buildup causes the other signs and symptoms of MCAD deficiency.